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 PMID:26531099  

ESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation.

Amruta Bhate | Darren J Parker | Thomas W Bebee | Jaegyoon Ahn | Waqar Arif | Edrees H Rashan | Sandip Chorghade | Anthony Chau | Jae-Hyung Lee | Sayeepriyadarshini Anakk | Russ P Carstens | Xinshu Xiao | Auinash Kalsotra
Nature communications | 2015

Although major genetic networks controlling early liver specification and morphogenesis are known, the mechanisms responsible for postnatal hepatic maturation are poorly understood. Here we employ global analyses of the mouse liver transcriptome to demonstrate that postnatal remodelling of the liver is accompanied by large-scale transcriptional and post-transcriptional transitions that are cell-type-specific and temporally coordinated. Combining detailed expression analyses with gain- and loss-of-function studies, we identify epithelial splicing regulatory protein 2 (ESRP2) as a conserved regulatory factor that controls the neonatal-to-adult switch of ∼20% of splice isoforms in mouse and human hepatocytes. The normal shift in splicing coincides tightly with dramatic postnatal induction of ESRP2 in hepatocytes. We further demonstrate that forced expression of ESRP2 in immature mouse and human hepatocytes is sufficient to drive a reciprocal shift in splicing and causes various physiological abnormalities. These findings define a direct role for ESRP2 in the generation of conserved repertoires of adult splice isoforms that facilitate terminal differentiation and maturation of hepatocytes.

Pubmed ID: 26531099

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM088809
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK050306
  • Agency: NHLBI NIH HHS, United States
    Id: R01HL126845
  • Agency: NHGRI NIH HHS, United States
    Id: R01HG006264
  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG006264
  • Agency: NIGMS NIH HHS, United States
    Id: R01-GM088809
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL126845
  • Agency: NIDDK NIH HHS, United States
    Id: P30-DK050306

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